# Autoantibodies to tumor-derived neoepitopes as biomarkers and immunoPET agents for the early detection of small cell lung cancer

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2024 · $613,760

## Abstract

Project Summary/Abstract
 Small-cell lung cancer (SCLC) kills over 30,000 Americans every year and has a dismal 5-year overall
survival rate of less than 7%. However, SCLC outcomes are greatly improved by early detection and intervention,
with a nearly 50% 5-year survival rate for patients diagnosed at an early stage. These discrepant outcomes
indicate that, by far, the majority of SCLC cases are diagnosed at later stages at which tumors rapidly become
resistant to therapy, with death quickly following. Thus, an effective early detection strategy is necessary that
both identifies cancer in people at high risk and facilitates non-invasive imaging that can confirm and delineate
small tumors to guide surgical resection and treatment. We have found that autoantibodies (AAb) are present in
the plasma of essentially all SCLC patients (much more common than in other major cancers) and have validated
at least 7 AAb-identified neoantigens expressed by SCLC tumors that can be exploited as highly cancer-specific
early detection biomarkers and/or imaging targets. We envision an early detection/diagnosis platform performed
during the recommended annual low-dose computed tomography (LD-CT) lung cancer screenings for heavy
smokers. However, LD-CT and all current imaging modalities are not suitable for SCLC early detection even in
smoking enriched populations due to lower than required sensitivity/specificity and risk/benefit analyses. Here,
we propose a two-tiered approach, with a blood test that detects the presence of AAb specific for SCLC that
would trigger immuno-positron emission tomography (immunoPET) imaging utilizing a radioimmunoconjugate
that specifically targets the autoantigenic proteins expressed only on SCLC tumors. The blood test ensures that
only high-risk individuals are screened and the immunoPET confirms and localizes the tumor for future treatment.
Thus, in Aim 1, we propose to define the role of SCLC-specific autoantigens (AAg), isolate human B cells specific
to the AAg, test the AAg as highly sensitive and specific early detection biomarkers, and sequence the AAb
variable regions and clone them into expression vectors to produce human monoclonal recombinant antibodies
for imaging purposes. In Aim 2, we propose to perform immunoimaging of SCLC tumors using fluorophore- and
radionuclide-labeled AAb immunoconjugates specific for these cancer targeted neoantigens/epitopes.
Preliminary data for the 2 antibodies that we have tested so far show that they specifically bind to SCLC tumors
in preclinical models, underscoring the feasibility of the entire pipeline. In summary, we will combine AAb-AAg
early detection for risk stratification with immunoPET imaging to confirm and localize tumors, thereby establishing
an early detection pathway capable of reducing the mortality of this highly aggressive cancer.

## Key facts

- **NIH application ID:** 10896444
- **Project number:** 5R01CA281801-02
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Delphine L Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $613,760
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896444

## Citation

> US National Institutes of Health, RePORTER application 10896444, Autoantibodies to tumor-derived neoepitopes as biomarkers and immunoPET agents for the early detection of small cell lung cancer (5R01CA281801-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10896444. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*